Citations

AbstractResearch demonstrates that patients with fibromyalgia who have higher positive and lower negative affect have lower symptom burden. Affect has been shown to be associated with resilience. This study examined the relationship between affect, resilience and fibromyalgia symptom burden in a clinical sample of patients with fibromyalgia. We hypothesized that (a) positive and negative affect would be associated with fibromyalgia symptom burden; (b) resilience would be associated with positive and negative affect; (c) resilience would be associated with fibromyalgia symptom burden; and (d) the connection between resilience and fibromyalgia symptom burden would be mediated by both positive and negative affect. A sample of 858 patients with fibromyalgia completed questionnaires. Mediation modelling revealed statistically significant direct effects of resilience on fibromyalgia symptom burden (β = −0.10, P < 0.001) and statistically significant indirect effects of resilience on fibromyalgia symptom burden through affect (β = −0.36, P < 0.001), suggesting that both resilience and affect influence fibromyalgia symptom burden. Our results suggest that improving affect through resiliency training could be studied as a modality for improving fibromyalgia symptom burden. Copyright © 2013 John Wiley & Sons, Ltd.

Insulin deprivation in type 1 diabetes (T1D) individuals increases lipolysis and plasma free fatty acids (FFA) concentration, which can stimulate synthesis of intramyocellular bioactive lipids such as ceramides (Cer) and long-chain fatty acid-CoAs (LCFa-CoAs). Ceramide was shown to decrease muscle insulin sensitivity, and at mitochondrial levels it stimulates reactive oxygen species production. Here, we show that insulin deprivation in streptozotocin diabetic C57BL/6 mice increases quadriceps muscle Cer content, which was correlated with a concomitant decrease in the body fat and increased plasma FFA, glycosylated hemoglobin level (%Hb A1c), and muscular LCFa-CoA content. The alternations were accompanied by an increase in protein expression in LCFa-CoA and Cer synthesis (FATP1/ACSVL5, CerS1, CerS5), a decrease in the expression of genes implicated in muscle insulin sensitivity (GLUT4, GYS1), and inhibition of insulin signaling cascade by Aktα and GYS3β phosphorylation under acute insulin stimulation. Both the content and composition of sarcoplasmic fraction sphingolipids were most affected by insulin deprivation, whereas mitochondrial fraction sphingolipids remained stable. The observed effects of insulin deprivation were reversed, except for content and composition of LCFa-CoA, CerS protein expression, GYS1 gene expression, and phosphorylation status of Akt and GYS3β when exogenous insulin was provided by subcutaneous insulin implants. Principal component analysis and Pearson's correlation analysis revealed close relationships between the features of the diabetic phenotype, the content of LCFa-CoAs and Cers containing C18-fatty acids in sarcoplasm, but not in mitochondria. Insulin replacement did not completely rescue the phenotype, especially regarding the content of LCFa-CoA, or proteins implicated in Cer synthesis and muscle insulin sensitivity. These persistent changes might contribute to muscle insulin resistance observed in T1D individuals.

ABSTRACTBackgroundA radial forearm free flap (RFFF) is used frequently in oral and pharyngeal reconstruction. Pseudoaneurysms within RFFFs and their management have not been previously reported.Methods and ResultsIn the present case, a patient with chemoradiation failure of the right base of the tongue clear cell carcinoma underwent salvage resection and failed reconstruction with pectoralis major muscle flap. He subsequently underwent RFFF reconstruction with delayed development of a radial artery pseudoaneurysm at the site of a previous arterial line within the RFFF, which was not present perioperatively. A rupture of this pseudoaneurysm manifested with recurrent bleeding. Angiography with embolization successfully arrested the bleeding without compromising the flap.ConclusionRuptured pseudoaneurysm of the radial artery within the RFFF is a rare and life‐threatening complication, which in the posterior oral cavity and pharynx can be effectively managed with angioembolization. © 2014 Wiley Periodicals, Inc. Head Neck 37: E12‐E14, 2015

Abstract Introduction: With an expanding population of patients requiring ventricular assist devices, it is inevitable that these patients will require noncardiac surgery. Ventricular assist devices provide mechanical support for a failing heart either as a bridge to transplant or now as a long-term support if transplant is not available, so-called destination therapy. These devices can add significant technical challenges to abdominal surgery, in that the power supply and drivelines crossing the abdomen can potentially be damaged. The use of preoperative or intraoperative imaging may aid in locating these devices and increase patient safety. Materials and Methods: We describe a laparoscopic cholecystectomy in two patients supported with HeartMate ® II (Thoratec Corp., Pleasanton, CA) left ventricular assist devices. Our use of fluoroscopic guidance in port placement is also described. A literature review was performed to assess the frequency of laparoscopic procedures performed on patients with similar ventricular assist devices and of complications associated with the device and other comorbidities. Results: Laparoscopic cholecystectomy was performed without significant intraoperative hemodynamic changes. The use of imaging, such as fluoroscopy, can identify the location of the ventricular assist device and its associated drive wires to assure they are not damaged intraoperatively. Conclusions: Laparoscopic cholecystectomy can be performed safely on patients with ventricular assist devices. Complications due to damage to the device can be avoided with the assistance of fluoroscopy to identify the implanted abdominal portions of the ventricular assist device. Each laparoscopic procedure performed on these patients presents the surgeon with unique obstacles in which careful operative planning and intraoperative monitoring are essential.

Key points A CO‐dependent transwall gradient of resting membrane potential exists across the circular muscle layer in the gastrointestinal tract; this gradient regulates the strength of phasic muscle contraction during electrical slow wave activity. H2S, CO and NO are endogenously generated in the muscle layers of the gut wall. Inhibiting the H2S producing enzyme CSE with the CSE inhibitor PAG had no significant effect on transwall resting membrane potential gradient in control preparations but significantly shifted the entire gradient in the depolarizing direction in preparations pretreated with the NO synthase (NOS) inhibitor l‐NNA. PAG significantly shifted the gradient in the depolarizing direction in mouse preparations lacking neuronal NOS (nNOS‐KO) and the gradient was significantly shifted in the depolarizing direction in mouse preparations lacking both nNOS and CSE (CSE‐KO–nNOS‐KO). NO production was significantly higher in CSE‐KO mouse preparations compared to wild‐type mouse preparations and the amplitude of NO‐mediated slow inhibitory junction potentials (S‐IJPs) was significantly higher in CSE‐KO mouse preparations compared to the amplitude of S‐IJPs in wild‐type mouse preparations. Nearly all submucosal neurons and myenteric neurons were CSE positive and 11% of submucosal neurons and 50% of myenteric neurons were nNOS positive. Our novel findings suggested that endogenous H2S is a stealth hyperpolarizing factor on smooth muscle cells and that endogenous H2S inhibits NO production from nNOS. AbstractA transwall gradient in resting membrane potential (RMP) exists across the circular muscle layer in the mouse colon. This gradient is dependent on endogenous generation of CO. H2S is also generated in muscle layers of the mouse colon. The effect of endogenously generated H2S on the transwall gradient is not known. The aim was to investigate the role of endogenous H2S. Our results showed that the CSE inhibitor dl‐propargylglycine (PAG, 500 μm) had no effect on the transwall gradient. However, in preparations pretreated with the nitric oxide synthase inhibitor N‐nitro‐l‐arginine (l‐NNA, 200 μm) and in nNOS‐knockout (KO) mouse preparations, PAG shifted the transwall gradient in the depolarizing direction. In CSE‐KO–nNOS‐KO mice, the gradient was shifted in the depolarizing direction. Endogenous generation of NO was significantly higher in muscle preparations of CSE‐KO mice compared to wild‐type (WT) mice. The amplitude of NO‐mediated slow inhibitory junction potentials (S‐IJPs) evoked by electric field stimulation was significantly higher in CSE‐KO mouse preparations compared to the amplitude of S‐IJPs in wild‐type mouse preparations. CSE was present in all submucosal ganglion neurons and in almost all myenteric ganglion neurons. Eleven per cent of CSE positive neurons in the submucosal plexus and 50% of CSE positive neurons in the myenteric plexus also contained nNOS. Our results suggest that endogenously generated H2S acts as a stealth hyperpolarizing factor on smooth muscle cells to maintain the CO‐dependent transwall gradient and inhibits NO production from nNOS.

Abstract Background Primary myelofibrosis ( PMF ), essential thrombocythemia ( ET ), and polycythemia vera ( PV ) are BCR ABL ‐negative myeloproliferative neoplasms ( MPN ). Published epidemiology data are scarce, and multiple sources are needed to assess the disease burden. Methods We assembled the most recent information available on the incidence and prevalence of myelofibrosis ( MF ), ET , and PV by conducting a structured and exhaustive literature review of the published peer‐reviewed literature in EMBASE and by reviewing online documentation from disease registries and relevant health registries in European countries. The search was restricted to human studies written in English or French and published between January 1, 2000, and December 6, 2012. Results Eleven articles identified from EMBASE , three online hematology or oncology registries, and two Web‐based databases or reports were used to summarize epidemiological estimates for MF , PV , and ET . The incidence rate of MF ranged from 0.1 per 100 000 per year to 1 per 100 000 per year. Among the various registries, the incidence of PV ranged from 0.4 per 100 000 per year to 2.8 per 100 000 per year, while the literature estimated the range of PV incidence to be 0.68 per 100 000 to 2.6 per 100 000 per year. The estimated incidence of ET was between 0.38 per 100 000 per year and 1.7 per 100 000 per year. While a few studies reported on the MPN s' prevalences, it is difficult to compare them as various types of prevalence were calculated (point prevalence vs. period prevalence) and standardization was made according to different populations (e.g., the world population and the European population). Conclusion There is a wide variation in both prevalence and incidence estimates observed across European data sources. Carefully designed studies, with standardized definitions of MPN s and complete ascertainment of patients including both primary and secondary MF s, should be conducted so that estimates of the population aimed to receive novel treatments for these neoplasms are better understood assist public health planning and provide valuable information about the burden of illness to policy makers, funding agencies, resource planners, healthcare insurers, and pharmaceutical manufacturers.

Purpose To compare American Joint Committee on Cancer (AJCC), International Union Against Cancer (UICC), and Brigham and Women's Hospital (BWH) tumor (T) staging systems for cutaneous squamous cell carcinoma and validate BWH staging against prior data. Patients and Methods Primary tumors diagnosed from 2000 to 2009 at BWH (n = 1,818) were analyzed. Poor outcomes (local recurrence [LR], nodal metastasis [NM], and disease-specific death [DSD]) were analyzed by T stage with regard to each staging system's distinctiveness (outcome differences between stages), homogeneity (outcome similarity within stages), and monotonicity (outcome worsening with increasing stage). Results AJCC and UICC T3 and T4 were indistinct with overlapping 95% CIs for 10-year cumulative incidences of poor outcomes, but all four BWH stages were distinct. AJCC and UICC high-stage tumors (T3/T4) were rare at 0.3% and 3% of the cohort, respectively. Most poor outcomes occurred in low stages (T1/T2; AJCC: 86% [95% CI, 77% to 91%]; UICC: 70% [61% to 79%]) resulting in heterogeneous outcomes in T1/T2. Conversely, in BWH staging, only 5% of tumors were high stage (T2b/T3), but they accounted for 60% (95% CI, 50% to 69%) of poor outcomes (70% of NMs and 83% of DSDs) indicating superior homogeneity and monotonicity as previously defined. Cumulative incidences of poor outcomes were low for BWH low-stage (T1/T2a) tumors (LR, 1.4% [95% CI, 1% to 2%]; NM, 0.6% [95% CI, 0% to 1%]; DSD, 0.2% [95% CI, 0% to 0.5%]) and higher for high-stage (T2b/T3) tumors (LR, 28% [95% CI, 19% to 38%]; NM, 25% [95% CI, 16% to 35%]; and DSD, 22% [95% CI, 13% to 34%]), which validated an earlier study of an alternative staging system. Conclusion BWH staging offers improved distinctiveness, homogeneity, and monotonicity over AJCC and UICC staging. Population-based validation is needed. BWH T2b/T3 tumors define a high-risk group requiring further study for optimal management.